Effects of Sacubitril/Valsartan Therapy on Biomarkers, My... | NCT02887183

Label	Type	Description	Intervention Names
LCZ696(sacubitril/valsartan)	Other	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.	Drug: LCZ696 (sacubitril/valsartan)

Name	Type	Description	Arm Group Labels	Other Names
LCZ696 (sacubitril/valsartan)	Drug	LCZ696 (sacubitril/valsartan) was supplied as unscored, ovaloid, film-coated oral tablets in the strengths of 24/26 mg, 49/51 mg, 97/103 mg to be taken twice daily (bid)

Measure	Description	Time Frame
Change in Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to One Year	Change in concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to one year	Baseline, one year
Change in Left Atrial Volume Index (LAVi), Left Ventricular End Diastolic Volume Index (LVEDVi), Left Ventricular End Systolic Volume Index (LVESVi), and From Baseline to One Year	Change in left atrial volume index (LAVi), left ventricular end diastolic volume index (LVEDVi), left ventricular end systolic volume index (LVESVi), and from baseline to one year	Baseline, one Year
Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to One Year	Change in Left ventricular ejection fraction (LVEF) from baseline to one year. LVEF is a measurement expressed as a percentage of how much blood the left ventricle pumps out with each contraction.	Baseline, one year
Change in Log-transformed NT-proBNP and Change in Structural Cardiac Measurements LVESVi, LVEDVi, LAVi, and LVEF From Baseline to One Year	Pearson's correlation coefficient was calculated between change in log-transformed NT-proBNP and change in structural cardiac measurements LVESVi, LVEDVi, LAVi, and LVEF from baseline to one year.	Baseline, one year

Measure	Description	Time Frame
Change in Log-transformed NT-proBNP Concentration and Change in Echocardiographic Measurements LVESVi, LVEDVi, LAVi, and LVEF From Baseline to Month 6	Pearson's correlation coefficient was calculated between change in log-transformed NT-proBNP and change in echocardiographic measurements LVESVi, LVEDVi, LAVi, and LVEF from baseline to Month 6	Baseline, Month 6

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Based on the USPI for sacubitril/valsartan, subjects eligible for inclusion in this study must fulfill all of the following criteria at screening and baseline:

Written informed consent must be obtained before any assessment is performed.
Men and women ≥ 18 years of age.
LVEF ≤ 40% subjects who are candidates for on-label sacubitril/valsartan treatment per standard of care.
New York Heart Association (NYHA) Functional class II-IV.
LVEF ≤40% via any local measurement within the past 6 months using echocardiography, multi gated acquisition scan (MUGA), CT scanning, MRI or ventricular angiography provided no subsequent study documenting an EF of >40%. If the EF measurement is expressed as a value range, the average of the range endpoint values should be used as the EF.
If a subject is on a loop diuretic, they must be on a stable dose for 2 weeks prior to baseline.

Key Exclusion Criteria:

Subjects fulfilling any of the following criteria, at screening and prior to dispensing of study drug, are not eligible for inclusion in this study. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible subjects/subjects.

pregnant or nursing women
women of child bearing potential not using highly effective method of contraception during dosing and for 7 days after stopping study medication
History of hypersensitivity to any of the study drugs, including history of hypersensitivity to drugs of similar chemical classes, or allergy to angiotensin converting enzyme inhibitor (ACEIs), Angiotensin II Receptor Blockers (ARBs), or Neutral endopeptidase (NEP) inhibitors as well as known or suspected contraindications to the study drugs.
History of angioedema drug related or otherwise.
Requirement of treatment with either ACE inhibitor and/or ARB.
Subjects with a heart transplant or ventricular assistance device (VAD) or intent to transplant (on transplant list) or implant a VAD.
Subjects with a cardio resynchronization therapy devices (CRT/CRT-D) implanted within 6 months of screening visit.
Subjects who are currently taking inotropic agents.
Current or prior treatment with sacubitril/valsartan.
Subjects taking medications prohibited by the protocol.
Subjects with diabetes mellitus who are taking aliskiren.
Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days until the expected pharmacodynamic effect has returned to baseline, whichever is longer.
Concomitant use of nesiritide.
Bile acid sequestering agents such as cholestyramine or colestipol are prohibited to avoid interference with study drug absorption.
Any hospital admission/discharge related to heart failure within 2 weeks prior to baseline.
The use of outpatient or inpatient i.v. diuretic therapy within 2 weeks prior to baseline.
Enrollment in another clinical trial within 30 days of screening.
Potassium > 5.2 mEq/L at screening.
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within one year.

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Birmingham	Alabama	35243	United States
Novartis Investigative Site

PubMed Identifier	Type	Citation	Retractions
37816446	Derived	Omar AMS, Murphy S, Felker GM, Pina I, Butler J, Liu Y, Mohebi R, Bhatia K, Ward JH, Williamson KM, Solomon SD, Januzzi JL, Contreras J. Isovolumic Contraction Velocity in Heart Failure With Reduced Ejection Fraction and Effect of Sacubitril/Valsartan: the PROVE-HF Study. J Card Fail. 2024 May;30(5):653-665. doi: 10.1016/j.cardfail.2023.10.001. Epub 2023 Oct 8.
37401523

Label	URL
A Plain Language Trial Summary is available on novartisclinicaltrials.com	View source

ID	Title	Description
FG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 27, 2018	Oct 17, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to One Year

Change in concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to one year

Full Analysis Set

Posted

Geometric Mean

Full Range

pg/mL

Baseline, one year

ID	Title	Description
OG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Units	Counts
Participants	OG000794

Title

Denominators

Categories

Title	Measurements
	OG0000.5905(0.5470 to 0.6375)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		ANCOVA		<.0001		Least Squared Geometric Mean Ratio	0.6320			2-Sided	95	0.5865	0.6810					Other

Primary

Change in Left Atrial Volume Index (LAVi), Left Ventricular End Diastolic Volume Index (LVEDVi), Left Ventricular End Systolic Volume Index (LVESVi), and From Baseline to One Year

Change in left atrial volume index (LAVi), left ventricular end diastolic volume index (LVEDVi), left ventricular end systolic volume index (LVESVi), and from baseline to one year

Full Analysis Set

Posted

Mean

Standard Deviation

mL/m^2

Baseline, one Year

ID	Title	Description
OG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Units	Counts
Participants	OG000

Primary

Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to One Year

Change in Left ventricular ejection fraction (LVEF) from baseline to one year. LVEF is a measurement expressed as a percentage of how much blood the left ventricle pumps out with each contraction.

Full Analysis Set

Posted

Mean

Standard Deviation

Percentage

Baseline, one year

ID	Title	Description
OG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Units	Counts
Participants	OG000

Primary

Change in Log-transformed NT-proBNP and Change in Structural Cardiac Measurements LVESVi, LVEDVi, LAVi, and LVEF From Baseline to One Year

Pearson's correlation coefficient was calculated between change in log-transformed NT-proBNP and change in structural cardiac measurements LVESVi, LVEDVi, LAVi, and LVEF from baseline to one year.

Full Analysis Set

Posted

Number

95% Confidence Interval

Pearson's Correlation

Baseline, one year

ID	Title	Description
OG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Units	Counts
Participants	OG000

Secondary

Change in Log-transformed NT-proBNP Concentration and Change in Echocardiographic Measurements LVESVi, LVEDVi, LAVi, and LVEF From Baseline to Month 6

Pearson's correlation coefficient was calculated between change in log-transformed NT-proBNP and change in echocardiographic measurements LVESVi, LVEDVi, LAVi, and LVEF from baseline to Month 6

Full Analysis Set

Posted

Number

95% Confidence Interval

Pearson's Correlation

Baseline, Month 6

ID	Title	Description
OG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) and Change in Change in Left Atrial Volume Index (LAVi) by Selected Groups of Interest at Month 6

Pearson's correlation coefficient to examine the association between change in log-transformed NT-proBNP and LAVi from baseline to 6 months overall in subgroups of interest, these subgroups are:

Subjects with HFrEF and "low" NT-proBNP (<600 if not hospitalized or <400 if hospitalized) or "low" BNP (<150 if not hospitalized, <100 if hospitalized) at baseline.
Subjects with new onset HF and/or RAAS naïve.
Subjects who are not receiving the target sacubitril/valsartan dose.

Full Analysis Set

Posted

Number

95% Confidence Interval

Pearson's Correlation Coefficient

Baseline, Month 6

ID	Title	Description
OG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Units	Counts

Secondary

Change From Baseline in Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) and Change in Left Ventricular End Systolic Volume Index (LVESVi) by Selected Groups of Interest at Month 6

Pearson's correlation coefficient to examine the association between change in log-transformed NT-proBNP and LVESVi from baseline to 6 months overall in subgroups of interest, these subgroups are:

Subjects with HFrEF and "low" NT-proBNP (<600 if not hospitalized or <400 if hospitalized) or "low" BNP (<150 if not hospitalized, <100 if hospitalized) at baseline.
Subjects with new onset HF and/or RAAS naïve.
Subjects who are not receiving the target sacubitril/valsartan dose.

Full Analysis Set

Posted

Number

95% Confidence Interval

Pearson's Correlation Coefficient

Baseline, Month 6

ID	Title	Description
OG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Units	Counts

Secondary

Change From Baseline in Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) and Change in Left Ventricular End Diastolic Volume Index (LVEDVi) by Selected Groups of Interest at Month 6

Pearson's correlation coefficient to examine the association between change in log-transformed NT-proBNP and LVEDVi from baseline to 6 months overall in subgroups of interest, these subgroups are:

Subjects with HFrEF and "low" NT-proBNP (<600 if not hospitalized or <400 if hospitalized) or "low" BNP (<150 if not hospitalized, <100 if hospitalized) at baseline.
Subjects with new onset HF and/or RAAS naïve.
Subjects who are not receiving the target sacubitril/valsartan dose.

Full Analysis Set

Posted

Number

95% Confidence Interval

Pearson's Correlation Coefficient

Baseline, Month 6

ID	Title	Description
OG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Units	Counts

Secondary

Change From Baseline in Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) and Change in Left Ventricular Ejection Fraction (LVEF) by Selected Groups of Interest at Month 6

Pearson's correlation coefficient to examine the association between change in log-transformed NT-proBNP and LVEF from baseline to 6 months overall in subgroups of interest, these subgroups are:

Subjects with HFrEF and "low" NT-proBNP (<600 if not hospitalized or <400 if hospitalized) or "low" BNP (<150 if not hospitalized, <100 if hospitalized) at baseline.
Subjects with new onset HF and/or RAAS naïve.
Subjects who are not receiving the target sacubitril/valsartan dose.

Full Analysis Set

Posted

Number

95% Confidence Interval

Pearson's Correlation Coefficient

Baseline, Month 6

ID	Title	Description
OG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Units	Counts

Secondary

Mean Change in the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) Clinical Summary Score From Baseline to Month 12

The KCCQ-23 is a self-administered questionnaire and requires, on average, 4-6 minutes to complete. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and Quality of Life (QoL). A change of 5 points on the scale scores, either as a group mean difference or an intra-individual change appears to be clinically significant, based on comparisons of changes in the scale scores to clinical indicators and subject global reports of change. The analysis will be done for groups of subjects with N-terminal pro-brain natriuretic peptide<1000 pg/mL and N-Terminal pro-brain natriuretic peptide>=1000 pg/mL at Month 12.

Full Analysis Set

Posted

Mean

Standard Deviation

Points on a scale

Baseline, month 12

ID	Title	Description
OG000	LCZ696(Sacubitril/Valsartan)	Subjects received sacubitril/valsartan (LCZ696) on Day 1. The initial dose was determined by the investigator and per the approved indication described in the United States prescribing information/package insert (USPI). The three doses available were: 24/26 mg (Dose Level 1), 49/51mg (Dose Level 2) and 97/103mg (Dose Level 3). Titration of the dosage were performed per USPI at 2 to 4 week intervals as clinically tolerated until maximal tolerated or target dosage was achieved. Target dosage was sacubitril/valsartan 97/103 mg twice daily.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0005 affected794 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Acute left ventricular failure	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0007 affected794 at risk
Angina pectoris	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0008 affected794 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0008 affected794 at risk
Atrial flutter	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Atrial thrombosis	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Bradycardia	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Cardiac arrest	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0004 affected794 at risk
Cardiac failure	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG00014 affected794 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0006 affected794 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG00060 affected794 at risk
Cardiac perforation	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Cardiac ventricular thrombosis	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Cardiogenic shock	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Cardiomyopathy	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0006 affected794 at risk
Cardiorenal syndrome	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Left ventricular failure	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG00014 affected794 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Myocardial infarction	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Pericardial effusion	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pericarditis	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Sinus tachycardia	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0005 affected794 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG0008 affected794 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (21.1)	Systematic Assessment	EG00012 affected794 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0005 affected794 at risk
Ascites	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Colitis	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Constipation	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0005 affected794 at risk
Dysphagia	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Enteritis	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Gastritis	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0005 affected794 at risk
Gastrointestinal necrosis	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Ileus	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Incarcerated umbilical hernia	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Intestinal pseudo-obstruction	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Melaena	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Nausea	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Peptic ulcer	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Retroperitoneal mass	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Spigelian hernia	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Vomiting	Gastrointestinal disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Asthenia	General disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Chest pain	General disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Death	General disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Fatigue	General disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Hernia	General disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Medical device site haematoma	General disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Non-cardiac chest pain	General disorders	MedDRA (21.1)	Systematic Assessment	EG00013 affected794 at risk
Oedema peripheral	General disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Pain	General disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Peripheral swelling	General disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Physical deconditioning	General disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pyrexia	General disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hepatitis toxic	Hepatobiliary disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Abscess oral	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Arthritis bacterial	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Atypical pneumonia	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Bacterial sepsis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Bronchitis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Bronchitis viral	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Cellulitis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0004 affected794 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Corona virus infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Device related infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Diverticulitis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Gastroenteritis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hepatitis C	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Influenza	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Localised infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Osteomyelitis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0006 affected794 at risk
Periorbital cellulitis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pneumonia	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG00020 affected794 at risk
Pneumonia bacterial	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pneumonia viral	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pyelonephritis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Respiratory syncytial virus infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Sepsis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0007 affected794 at risk
Septic shock	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0004 affected794 at risk
Staphylococcal infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Streptococcal infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Streptococcal sepsis	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Urinary tract infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0007 affected794 at risk
Vascular device infection	Infections and infestations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Brain herniation	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Extradural haematoma	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0005 affected794 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Alanine aminotransferase increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Liver function test increased	Investigations	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0005 affected794 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Fluid retention	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Gout	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hyperammonaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0009 affected794 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0006 affected794 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Fasciitis	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Gouty arthritis	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Spondylitis	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Vertebral osteophyte	Musculoskeletal and connective tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Bladder transitional cell carcinoma stage II	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Bone cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Lung carcinoma cell type unspecified stage IV	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Ataxia	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Carotid artery disease	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Cerebral infarction	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0004 affected794 at risk
Dizziness	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0004 affected794 at risk
Embolic cerebral infarction	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Encephalopathy	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Ischaemic cerebral infarction	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Lethargy	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Lumbosacral radiculopathy	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Presyncope	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Seizure	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Syncope	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG00011 affected794 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Device failure	Product Issues	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Device malfunction	Product Issues	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Alcohol withdrawal syndrome	Psychiatric disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Bipolar disorder	Psychiatric disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Depression	Psychiatric disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Drug abuse	Psychiatric disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Mental status changes	Psychiatric disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG00023 affected794 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
End stage renal disease	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Haematuria	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Renal failure	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Renal injury	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Urinary retention	Renal and urinary disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG00010 affected794 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0009 affected794 at risk
Chronic respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0006 affected794 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hypercapnia	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0004 affected794 at risk
Laryngospasm	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pulmonary alveolar haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG0002 affected794 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (21.1)	Systematic Assessment	EG00010 affected794 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Stasis dermatitis	Skin and subcutaneous tissue disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Resuscitation	Surgical and medical procedures	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Aortic aneurysm	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Aortic stenosis	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Circulatory collapse	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Haematoma	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hypertensive crisis	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Hypotension	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG00011 affected794 at risk
Hypovolaemic shock	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Labile blood pressure	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Orthostatic hypotension	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Pelvic venous thrombosis	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Peripheral artery stenosis	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk
Peripheral ischaemia	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0003 affected794 at risk
Peripheral venous disease	Vascular disorders	MedDRA (21.1)	Systematic Assessment	EG0001 affected794 at risk

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases

ID	Term
D013777	Tetrazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D014633	Valine
D000597	Amino Acids, Branched-Chain
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000601	Amino Acids, Essential

ID	Term
C549068	sacubitril and valsartan sodium hydrate drug combination
C000717211	sacubitril
D000068756	Valsartan